The metabolic syndrome relates to a combination of disorders which is found at high prevalence in many populations, and which consequently presents a major global health challenge. Metabolic syndrome is particularly characterised by hyperglycemia hypertension, hypertriglyceridaemia and obesity, and has been linked to cardiovascular disease and diabetes.
Fasting hyperglycemia, i.e. elevated blood glucose, is an important characteristic of metabolic syndrome. Subjects showing the metabolic syndrome may vary in the degree of hyperglycemia, and the severity of this condition may progress over time. Thus the hyperglycemia found in metabolic syndrome patients may result from a condition classified as impaired fasting glucose, impaired glucose tolerance or insulin resistance.
Many patients with metabolic syndrome are diagnosed with full type 2 diabetes mellitus (adult-onset diabetes). Type 2 diabetes is characterised by a fasting plasma glucose level of 7.0 mmol/l or higher. Type 2 diabetes is commonly caused by insulin resistance coupled with a deficiency in pancreatic insulin production. Uncontrolled diabetes may result in serious complications such as neuropathy, retinopathy and nephropathy. Diabetic retinopathy is a major cause of blindness in the developed world. Insulin resistance is thus closely associated with both the metabolic syndrome and diabetes mellitus, as well as its complications.
Insulin resistance is also linked to abnormalities in blood lipids, such as a high level of free fatty acids and triglycerides, which are commonly found together in metabolic syndrome. These factors, together with high LDL cholesterol, low HDL cholesterol and high blood pressure are major risk factors for the development of atherosclerosis and consequently various cardiovascular disorders. Many of the above factors are typically present in subjects with metabolic syndrome, leading to an increased incidence of conditions such as coronary heart disease and stroke.
Coronary heart disease is a condition typically caused by narrowing and hardening of the coronary arteries (atherosclerosis). Atherosclerosis may result from accumulation of cholesterol within the walls of the coronary arteries. Coronary heart disease may lead to a heart attack (myocardial infarction), heart failure or chest pain (angina pectoris). Coronary atherosclerosis, and thus diseases such as congestive heart failure, are closely associated with the metabolic syndrome, as well as elevated LDL cholesterol and cigarette smoking. The individual risk factors present in the metabolic syndrome combine to greatly raise the risk for coronary heart disease.
The glucocorticoid hormones (cortisol, corticosterone) produced by the adrenal gland also have the potential to cause insulin resistance. Cushing's disease, which results from overproduction of glucocorticoids, commonly leads to insulin resistance and type 2 diabetes. Some patients treated with glucocorticoids, e.g. as anti-inflammatory agents, also show insulin resistance. 11β-hydroxysteroid dehydrogenases (11β-HSDs) catalyse the interconversion of active glucocorticoids such as cortisol and their inert forms such as cortisone. Whereas 11β-HSD type 1 is a predominant reductase in most intact cells which generates active cortisol from cortisone, 11β-HSD type 2 is a high affinity dehydrogenase that rapidly inactivates cortisol in kidney and colon.
A large number of therapies are available for controlling conditions associated with metabolic syndrome. For instance, ACE inhibitors and diuretics are commonly used to lower blood pressure and statins (HMG-CoA reductase inhibitors) have been shown to be effective in lowering LDL cholesterol. In many cases, the metabolic syndrome and its associated conditions can be alleviated by non-pharmacological interventions, such as a combination of improved diet, exercise and weight loss. However, a major problem is that metabolic syndrome, and in particular serious associated disorders and complications such as hypertension and diabetic retinopathy, often go undetected for long periods of time. Many patients only present for treatment at a stage when serious irreversible damage has been done. Even when subjects are clinically assessed for the first time, there is often a lack of quantitative methods for accurately assessing the progression and severity of particular disorders.
There is therefore a need for improved methods for assessing susceptibility of subjects to conditions associated with metabolic syndrome.